Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemia

We describe the cases of two patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase d eveloped during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome ab normalities, that is, monosomies 9, 14, and 22, and by a clustered amplific ation of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusi on gene were integrated into the short arm of structurally abnormal chromos omes 17 in both patients. The conformity of these genetic features in two p atients with a rare disease manifestation leads us to the assumption that e ither the clustered amplification of the BCR/ABL fusion gene or the integra tion of this cluster into the short arm of chromosome 17 or both are associ ated with extramedullar disease progression in CML. Furthermore, the insert ion of amplified BCR/ABL fusion genes into structurally abnormal chromosome s provides a novel mechanism of disease progression in BCR/ABL-positive CML . (C) 2001 Wiley-Liss, Inc.